Although highly active antiretroviral therapy (HAART) effectively suppresses HIV replication, it is now clear that it cannot completely eradicate HIV from infected individuals. We have also recently begun to appreciate more fully the scope of toxicities and inconveniences associated with HAART medications leading to difficulties with adherence. Thus, long-term use of HAART may be problematic in many HIV-infected individuals. These realizations have led to a search for strategies to shift the focus from eradication to suppression of HIV replication while reducing toxicity and enhancing compliance. One approach to achieve these goals is to attempt to find strategies that allow for prolonged periods off HAART medications. Recently, Trimeris corporation has developed T-20, an inhibitor of HIV fusion to T-cells, a step required to spread virus from cell to cell. This new class of therapy, which has little recognized toxicity, could be used to allow patients to discontinue HAART medications for prolonged periods of time. In this intent to treat pilot study, we propose to evaluate the ability of T-20 to slow or prevent rebound of plasma HIV RNA when HAART medications are interrupted for a single 6 week period. The information obtained through this investigation could provide important insights into novel therapeutic strategies for HIV infection.